Topiramate Reduces Cocaine Use in Dependent Patients

By Anne Harding

NEW YORK - Topiramate was better than placebo for reducing cocaine use in a recently published randomized trial.

Cocaine-dependent patients on topiramate showed a significantly greater reduction from baseline in the proportion of non-use days per week compared to patients on placebo. Their likelihood of cocaine-free weeks was also significantly greater.

"This is the first time we've been able to establish a treatment for cocaine dependence," Dr. Bankole Johnson of the University of Maryland School of Medicine in Baltimore, the lead author of the new study, told Reuters Health.

Topiramate has been shown to help treat alcohol dependence and methamphetamine addiction, Dr. Johnson and his team noted in a paper online October 16 in JAMA Psychiatry. Small studies have also suggested that it may help reduce cocaine craving and cocaine use.

"The drug works by altering the effects of two transmitter systems. One of them is GABA and the other is glutamate," Dr. Johnson explained in an interview. "The GABA/glutamate balance in the brain affects how a third neurotransmitter works, which is dopamine. By altering that balance, you're able to produce a drug that reduces the drive or the craving for cocaine."

Dr. Johnson and his colleagues conducted a randomized, controlled trial in 142 cocaine-dependent patients. The medication was titrated for the first six weeks of the trial, up to 300 mg/day, and efficacy was tested for the following six weeks. Thirty-eight patients in the topiramate group and 34 in the placebo group completed the trial.

Patients visited the clinic three times per week, providing urine samples and receiving medication or placebo, and also received counseling.

Topiramate was more effective than placebo for the study's primary outcome, of increasing patients' mean weekly proportion of cocaine non-use days. The reduction from baseline was 13.3% for patients on topiramate, vs 5.3% for those on the placebo (p=0.02).

For the secondary outcome, increasing the likelihood of urinary cocaine-free weeks, the topiramate group showed a 16.6% increase from baseline, vs 5.8% for the placebo group (p=0.02).

There was also a greater reduction in several measurements of craving for the drug among the patients on topiramate, who also showed greater improvements on the Clinical Global Impression Observer Scale.

Side effects of topiramate can include mental slowing, difficulty concentrating, and memory lapses, Dr. Johnson noted.

"Most of the side effects of topiramate do improve over time. The key is that the medication needs to be given slowly, otherwise the patients do develop significant side effects," he said. "We didn't see very much of that in our study. The reason we didn't see very much of that is we titrated it in very slowly."

The findings show, Dr. Johnson said, "that patients who are quite medium to heavily dependent on cocaine can be treated well as outpatients, and that this can be a treatment that can be used to sustain a reduction in their cocaine use."

Dr. Kyle Kampman of the University of Pennsylvania in Philadelphia, who conducted the first pilot study of topiramate for cocaine dependence, said of Dr. Johnson's study, "What's really neat about topiramate is he found it seemed to produce a long period of abstinence, which is what I found too."

Dr. Kampman, who has also studied the drug in patients with both alcohol and cocaine dependence, added, "There haven't been that many medications for the treatment of cocaine dependence that have had multiple positive trials. Topiramate is among that small group, so I think it's promising."

Topiramate is already being used off-label to treat cocaine dependence, Dr. Kampman added.

In clinical trials of medication for treating drug dependence, Dr. Kampman said, psychotherapy is typically kept to a minimum. "We want to give enough psychotherapy to help hold the patients in treatment and treat them well, but whether or not topiramate would work better with a stronger type of psychotherapy, we don't know that," he said. "Seeing people once a week in cognitive behavioral therapy may not be optimal for the treatment of cocaine dependence with a medication, but that's a question for later studies."

SOURCE: https://bit.ly/1ic7mGY

JAMA Psychiatry 2013.